Chemical induction of the interaction between AIMP2-DX2 and Siah1 to enhance ubiquitination.

AIMP2-DX2 (hereafter DX2) is an oncogenic variant of aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) that mediates tumorigenic interactions with various factors involved in cancer. Reducing the levels of DX2 can effectively inhibit tumorigenesis. We previously reported that DX2 can be degraded through Siah1-mediated ubiquitination. In this study, we identified a compound, SDL01, which enhanced the interaction between DX2 and Siah1, thereby facilitating the ubiquitin-dependent degradation of DX2. SDL01 was found to bind to the pocket surrounding the N-terminal flexible region and GST domain of DX2, causing a conformational change that stabilized its interaction with Siah1. Our findings demonstrate that protein-protein interactions (PPIs) can be modulated through chemically induced conformational changes.

Furthering decent work by expanding the role of occupational safety and health.

BACKGROUND: The International Labour Organization (ILO) and the United Nations (UN) have promoted the concept of decent work as a Sustainable Development Goal for 2030 to address critical global problems. Occupational safety and health (OSH) are components of decent work, primarily through the ILO social protection objective of the goal, and are linked to various other objectives. OBJECTIVE: This Commentary applies a previously published staging framework to stimulate thinking about how the OSH field can contribute further to the achievement of decent work. METHODS: To advance the contribution of the framework, the different functions of OSH (research, practice, advocacy, governance, and professional education) were used to identify impediments to achieving decent work and develop recommendations for each determinant in the framework. RESULTS: Promoting and achieving decent work are complex issues that require a multifactorial approach. Numerous recommendations supporting systems thinking and transdisciplinary approaches are provided. CONCLUSIONS: The OSH field can expand to further address decent work.

Hypoxia-Regulated Proteins: Expression in Endometrial Cancer and Their Association with Clinicopathologic Features.

BACKGROUND: Hypoxia-regulated proteins (HIF-1α and GLUT-1) have been identified as prognostic markers in various cancers; however, their role in endometrial cancer remains unclear. This study aimed to evaluate HIF-1α and GLUT-1 expression in endometrial cancer and correlate their expression with clinicopathological features. MATERIALS AND METHODS: A tissue microarray (TMA) was constructed using specimens from a retrospective cohort of 51 endometrial cancer patients who underwent hysterectomy at the Gyeongsang National University Hospital between 2002 and 2009. Clinicopathologic data were collected from electronic medical records, and HIF-1α and GLUT-1 expressions were assessed in the tumor tissue. RESULTS: GLUT-1 expression in endometrial cancer was categorized as mosaic, central, or diffuse. Most patients (56.0%) exhibited a central pattern, followed by diffuse (32.0%) and mosaic (12.0%) patterns. GLUT-1 expression was not significantly associated with histologic grade (p = 0.365). HIF-1α expression in immune cells, but not tumor cells, was significantly associated with a higher histologic grade. A higher proportion of HIF-1α-positive immune cells, using both thresholds (≤1% vs. >1% and ≤5% vs. >5%), was significantly associated with higher histologic grade (p = 0.032 and p = 0.048, respectively). In addition, a higher proportion of HIF-1α-positive immune cells was significantly associated with a diffuse GLUT-1 expression pattern using >5% as a threshold. There were no significant differences in the proportion of HIF-1α-positive immune cells between groups stratified by age, tumor size, or invasion depth, regardless of whether the 1% or 5% threshold for HIF-1α positivity was used. CONCLUSIONS: A higher proportion of HIF-1α-positive immune cells is associated with endometrial cancers with higher histologic grade and diffuse GLUT1 expression patterns. These findings suggest a potential role for HIF-1α as a prognostic marker and highlight the need for further studies into the role of HIF-1α in the tumor microenvironment.

Outcomes of hematopoietic stem cell transplantation in patients with SARS-CoV-2 infection during the Omicron era.

Here, we present the outcomes of four patients with COVID-19 who underwent hematopoietic stem cell transplantation (HSCT) at the National Cancer Center in South Korea. Despite concerns about the unfavorable course of COVID-19 in HSCT recipients, none of our patients experienced severe COVID-19. Moreover, extended viral shedding in case 1, lasting over 100 days, was resolved after successful engraftment. Contracting the virus when the host could not mount enough of an immune reaction might result in a paradoxically favorable course. Vaccination, monoclonal antibodies, and antiviral agent usage against COVID-19 might also be effective. We suggest, if necessary, HSCT should not be deferred in COVID-19 patients.

Joint ICOH-WOPS & APA-PFAW global roundtable perspectives: exploring national policy approaches for psychological health at work through the 'National Policy Index' lens.

Worker psychological health is a significant global imperative which requires national policy action and stakeholder engagement. While national policy is a critical lever for improving worker psychological health, some countries are more progressive than others in relation to policy development and/or implementation. At the Joint Congress of the International Commission on Occupational Health, Scientific Committee on Work Organization and Psychosocial Factors and the Asia Pacific Academy for Psychosocial Factors Work in Tokyo (September 2023), a Global Roundtable was designed to initiate international dialogue and knowledge exchange regarding relevant national policy approaches. The Global Roundtable involved experts from diverse regions alongside an engaged audience of congress attendees and facilitators. Qualitative data were analysed against the five components of the National Policy Index tool, comprising policy priority, specific laws, nation-wide initiatives, sector-oriented initiatives, national survey and/or studies. Analysis revealed that while work-related psychological health is a policy priority across many countries, at the same time, there are global gaps in both legislation specificity and active regulation across different countries. For future policy development across countries, it will be beneficial to continue and deepen international discourse and for countries to share their approaches with others.

Reduction of GaAs Buffer Thickness and Its Impact on Epitaxially Integrated III-V Quantum Dot Lasers on a Si Substrate.

Monolithic integration of III-V quantum dot (QD) lasers onto a Si substrate is a scalable and reliable approach for obtaining highly efficient light sources for Si photonics. Recently, a combination of optimized GaAs buffers and QD gain materials resulted in monolithically integrated butt-coupled lasers on Si. However, the use of thick GaAs buffers up to 3 µm not only hinders accurate vertical alignment to the Si optical waveguide but also imposes considerable growth costs and time constraints. Here, for the first time, we demonstrate InAs QD lasers epitaxially grown on a 700 nm thick GaAs/Si template, which is approximately four times thinner than the conventional III-V buffers on Si. The optimized 700 nm GaAs buffer yields a remarkably smooth surface and low threading dislocation density of 4 × 108 cm-2, which is sufficient for QD laser growth. The InAs QD lasers fabricated on these ultrathin templates still lase at room temperature with a threshold current density of 661 A/cm2 and a characteristic temperature of 50 K. We believe that these results are important for the monolithically integrated III-V QD lasers for Si photonics applications.

plantMASST - Community-driven chemotaxonomic digitization of plants.

Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.

Drawing Guideline for JKMS Manuscripts (06): Scatter Plot.

The appropriate plot effectively conveys the author's conclusions to the readers. Journal of Korean Medical Science is providing a series of guidelines to show you how to make consistent and excellent plots more easily. In this article, we introduce scatter plots and more.

Association Between Flexible Work Arrangement and Sleep Problems Among Paid Workers: Using 6th Korean Working Conditions Survey.

Background: As social distancing persists and interest in work-life balance grows, more companies are adopting flexible work policies. While there have been studies on sleep disorders associated with different types of work, such as shift work, research exploring the relationship between flexible work schedules and sleep disorders is still limited, particularly among Korean workers. Methods: We performed a secondary analysis of the 6th Korean Working Conditions Survey, focusing on 31,243 paid workers out of a total of 50,538 participants. We defined flexible workers as those who set their own working hours. Sleep disorders were divided into three categories: 'difficulty falling asleep,' 'frequent waking during sleep,' and 'waking up feeling exhausted and fatigued.' Using scores derived from three specific symptoms, the Minimal Insomnia Symptoms Scale (MISS) was calculated to assess the prevalence of insomnia. We used chi-square tests to analyze demographic and job-related differences. A multivariate logistic regression analysis was employed to identify any relationship between flexible work schedules and sleep disorders. Results: Significant differences were found between flexible and non-flexible workers regarding age, income level, education level, and job type. Flexible workers reported sleep-related symptoms significantly more often. The odds ratio for insomnia was 1.40 (95% CI 1.21-1.61). For males, the odds ratio was 1.68 (1.36-2.08). Conclusion: This study establishes a correlation between flexible work schedules and sleep disorders among Korean salaried workers. Potential causes could include changes in circadian rhythm, increased work demands, and extended working hours. To precisely determine causality and associated diseases, further research is required.

Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases.

Genetic neuromuscular diseases are clinically and genetically heterogeneous genetic disorders that primarily affect the peripheral nerves, muscles, and neuromuscular junctions. This study aimed to identify pathogenic variants, calculate carrier frequency, and predict the genetic prevalence of autosomal recessive neuromuscular diseases (AR-NMDs). We selected 268 AR-NMD genes and analyzed their genetic variants sourced from the gnomAD database. After identifying the pathogenic variants using an algorithm, we calculated the carrier frequency and predicted the genetic prevalence of AR-NMDs. In total, 10,887 pathogenic variants were identified, including 3848 literature verified and 7039 manually verified variants. In the global population, the carrier frequency of AR-NMDs is 32.9%, with variations across subpopulations ranging from 22.4% in the Finnish population to 36.2% in the non-Finnish European population. The predicted genetic prevalence of AR-NMDs was estimated to be 24.3 cases per 100,000 individuals worldwide, with variations across subpopulations ranging from 26.5 to 41.4 cases per 100,000 individuals in the Latino/Admixed American and the Ashkenazi Jewish populations, respectively. The AR-NMD gene with the highest carrier frequency was GAA (1.3%) and the variant with the highest allele frequency was c.-32-13 T>G in GAA with 0.0033 in the global population. Our study revealed a higher-than-expected frequency of AR-NMD carriers, constituting approximately one-third of the global population, highlighting ethnic heterogeneity in genetic susceptibility.

Low-threshold 2†µm InAs/InP quantum dash lasers enabled by punctuated growth.

2 µm photonics and optoelectronics is promising for potential applications such as optical communications, LiDAR, and chemical sensing. While the research on 2 µm detectors is on the rise, the development of InP-based 2 µm gain materials with 0D nanostructures is rather stalled. Here, we demonstrate low-threshold, continuous wave lasing at 2 µm wavelength from InAs quantum dash/InP lasers enabled by punctuated growth of the quantum structure. We demonstrate low threshold current densities from the 7.1 µm width ridge-waveguide lasers, with values of 657, 1183, and 1944 A/cm2 under short pulse wave (SPW), quasi-continuous wave (QCW), and continuous wave operation. The lasers also exhibited good thermal stability, with a characteristic temperature T0 of 43 K under SPW mode. The lasing spectra is centered at 1.97 µm, coinciding with the ground-state emission observed from photoluminescence studies. We believe that the InAs quantum dash/InP lasers emitting near 2 µm will be a key enabling technology for 2 µm communication and sensing.

Beyond working hours: the association between long working hours, the use of work-related communication devices outside regular working hours, and anxiety symptoms.

OBJECTIVES: The present study aimed to identify and compare the associations between long working hours and use of work-related communication devices outside regular working hours and anxiety symptoms, thereby providing insight into redefining working hours. METHODS: Based on the cross-sectional data from the sixth Korean Working Conditions Survey (KWCS), specifically the responses from 46 055 workers, the use of work-related communication devices outside of regular working hours, long working hours, and anxiety symptoms were assessed. To investigate the associations between using work-related communication devices outside regular working hours or long working hours with anxiety symptoms, odds ratios (ORs) and 95% CIs were calculated using multiple logistic regression models. RESULTS: Among 46 055 participants, 25 659 (55.7%) used work-related communication devices outside working hours, 8145 (17.7%) worked long hours, and 2664 (5.8%) experienced anxiety symptoms. Compared with the reference group, those who used work-related communication devices outside regular working hours without working long hours, had higher OR of anxiety symptoms (OR: 2.18; 95% CI, 1.97-2.41) than those who worked long hours without using work-related communication devices during off-hours (OR: 1.32; 95% CI, 1.09-1.59). Furthermore, the group that both worked long hours and used work-related communication devices outside working hours exhibited the highest OR of anxiety symptoms (OR: 2.57; 95% CI, 2.24-2.97). CONCLUSIONS: Using work-related communication devices outside regular working hours is associated with a higher risk of anxiety symptoms compared with long working hours. This result suggests that using work-related devices outside regular working hours, in addition to regular work time, should be considered when redefining working hours.

Single-incision versus conventional multiport laparoscopic cholecystectomy in acute cholecystitis according to disease severity: single center retrospective study in Korea.

Purpose: The safety of single-incision laparoscopic cholecystectomy (SILC) for acute cholecystitis (AC) has not yet been confirmed. Methods: This single-center retrospective study included patients who underwent laparoscopic cholecystectomy (LC) for AC between April 2010 and December 2020. Propensity scores were used to match patients who underwent SILC with those who underwent conventional multiport LC (CMLC) in the entire cohort and in the two subgroups. Results: A total of 1,876 patients underwent LC for AC, and 427 (22.8%) underwent SILC. In the propensity score-matched analysis of the entire cohort (404 patients in each group), the length of hospital stay (2.9 days vs. 3.5 days, p = 0.029) was shorter in the SILC group than in the CMLC group. No significant differences were observed in other surgical outcomes. In grade I AC (336 patients in each group), the SILC group showed poorer surgical outcomes than the CMLC group, regarding operation time (57.6 minutes vs. 52.4 minutes, p = 0.001) and estimated blood loss (22.9 mL vs. 13.1 mL, p = 0.006). In grade II/III AC (58 patients in each group), there were no significant differences in surgical outcomes between the two groups. Postoperative pain outcomes were also not significantly different in the two groups, regardless of severity. Conclusion: This study demonstrated that SILC had similar surgical and pain outcomes to CMLC in patients with AC; however, subgroup analysis showed that SILC was associated with poor surgical outcomes than CMLC in grade I AC. Therefore, SILC should be carefully performed in patients with AC by experienced hepatobiliary surgeons.

HIF-1α inhibition by MO-2097, a novel chiral-free benzofuran targeting hnRNPA2B1.

INTRODUCTION: Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator mediating adaptive responses to hypoxia. It is up-regulated in the tumor microenvironment and recognized as an effective anticancer drug target. Previously, we discovered that the natural compound moracin-O and its synthetic derivative MO-460 inhibited HIF-1α via hnRNPA2B1. OBJECTIVES: This study aimed to develop novel HIF-1 inhibitors for cancer chemotherapy by harnessing the potential of the natural products moracins-O and P. METHODS: In an ongoing search for novel HIF-1 inhibitors, a series of nature-inspired benzofurans with modifications on the chiral rings of moracins-O and P were synthesized. They showed improved chemical tractability and were evaluated for their inhibitory activity on HIF-1α accumulation under hypoxic conditions in HeLa CCL2 cells. The most potent derivative's chemical-based toxicities, binding affinities, and in vivo anti-tumorigenic effects were evaluated. Further, we examined whether our compound, MO-2097, exhibited anticancer effects in three-dimensional cultured organoids. RESULTS: Herein, we identified a novel synthetic chiral-free compound, MO-2097, with reduced structural complexity and increased efficiency. MO-2097 exhibited inhibitory effects on hypoxia-induced HIF-1α accumulation in HeLa CCL2 cells via inhibition of hnRNPA2B1 protein, whose binding affinities were confirmed by isothermal titration calorimetry analysis. In addition, MO-2097 demonstrated in vivo efficacy and biocompatibility in a BALB/c mice xenograft model. The immunohistochemistry staining of MO-2097-treated tissues showed decreased expression of HIF-1α and increased levels of apoptosis marker cleaved caspase 3, confirming in vivo efficacy. Furthermore, we confirmed that MO-2097 works effectively in cancer patient-based organoid models. CONCLUSION: MO-2097 represents a promising new generation of chemotherapeutic agents targeting HIF-1α inhibition via hnRNPA2B1, requiring further investigation.

Reduction of Structural Defects in the GaSb Buffer Layer on (001) GaP/Si for High Performance InGaSb/GaSb Quantum Well Light-Emitting Diodes.

Monolithic integration of GaSb-based optoelectronic devices on Si is a promising approach for achieving a low-cost, compact, and scalable infrared photonics platform. While tremendous efforts have been put into reducing dislocation densities by using various defect filter layers, exploring other types of extended crystal defects that can exist on GaSb/Si buffers has largely been neglected. Here, we show that GaSb growth on Si generates a high density of micro-twin (MT) defects as well as threading dislocations (TDs) to accommodate the extremely large misfit between GaSb and Si. We found that a 250 nm AlSb single insertion layer is more effective than AlSb/GaSb strained superlattices in reducing both types of defects, resulting in a 4× and 13× reduction in TD density and MT density, respectively, compared with a reference sample with no defect filter layer. InGaSb quantum well light-emitting diodes were grown on the GaSb/Si templates, and the effect of TD density and MT density on their performance was studied. This work shows the importance of using appropriate defect filter layers for high performance GaSb-based optoelectronic devices on standard on-axis (001) Si via direct epitaxial growth.

The relationship between exposure to environmental noise and risk of atopic dermatitis, asthma, and allergic rhinitis.

BACKGROUND: Noise is defined as unwanted sound. It may induce negative emotions and mental health problems and may even lead to increased suicide risk. However, the impact of noise exposure on environmental diseases and disease severity is not well understood. This study aimed to elucidate the association between night-time noise exposure and the prevalence of environmental diseases in South Korea. METHODS: We conducted an analysis of the Environmental Disease Database provide by the National Health Insurance Service (NHIS) from 2013 to 2017. After spatially interpolating the noise data provided by the National Noise Information System (NNIS), night-time noise values in the district level were obtained by calculating the mean noise values at the administrative district level. The linear regression analyses were performed to test the association between the age-standardized prevalence ratio (SPR) and the night-time noise exposure in the district level. RESULTS: In areas with high night-time noise exposure (≥55 dB), the SPR for atopic dermatitis and allergic rhinitis were 1.0515 (95 % confidence interval [CI]:1.0508-1.0521) and 1.0202 (95 % CI:1.0201-1.0204), respectively, which were higher than those in the general population. The SPR for environmental diseases, including atopic dermatitis, asthma, and allergic rhinitis, was 1.0104 (95 % CI:1.0103-1.0105). Additionally, a significant linear association was observed between the level of nocturnal noise exposure and the total hospitalization period for atopic dermatitis (ß = 399.3, p < 0.01). CONCLUSION: We provide evidence of a significant association between night-time environmental noise and environmental diseases, particularly atopic dermatitis and allergic rhinitis. Furthermore, we observed a significant linear association between night-time noise exposure and the severity of atopic dermatitis.

Stereochemical assignment of clerodane-type diterpenes from the fruits of Casearia grewiifolia and their ability to inhibit PCSK9 expression.

More than 20 natural products have been reported to modulate PCSK9-mediated cholesterol regulation, and small-molecule-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors continue to be developed and identified. Here, twelve undescribed clerodane-type diterpenes (1-9 and 12-14) and two known compounds were isolated from the chloroform-soluble extract of the dried fruits of Casearia grewiifolia Vent. using a PCSK9 mRNA expression monitoring assay. Among the undescribed compounds, the stereochemistry of two diastereomeric grewiifolins A and B (1 and 2) were extensively elucidated using 2D Nuclear Overhauser Effect Spectroscopy (NOESY) experiments, excitation-sculptured indirect detection experiments (EXSIDE), interproton distance analyses, and computational calculations that included quantum chemical shift calculations combined with DP4+ analysis. All isolates were assessed for their inhibitory activity against PCSK9 and IDOL mRNA expression. Among the compounds tested, compound 3 inhibited PCSK9 and IDOL mRNA expression.

Acute cholecystitis in old adults: the impact of advanced age on the clinical characteristics of the disease and on the surgical outcomes of laparoscopic cholecystectomy.

BACKGROUND: Impact of advanced age on disease characteristics of acute cholecystitis (AC), and surgical outcomes after laparoscopic cholecystectomy (LC) has not been established. METHODS: This single-center retrospective study included patients who underwent LC for AC between April 2010 and December 2020. We analyzed the disease characteristics and surgical outcomes according to age: Group 1 (age < 60 years), Group 2 (60 ≤ age < 80 years), and Group 3 (age ≥ 80 years). Risk factors for complications were assessed using logistic regression analysis. RESULTS: Of the 1,876 patients (809 [43.1%] women), 723 were in Group 1, 867 in Group 2, and 286 in Group 3. With increasing age, the severity of AC and combined common bile duct stones increased. Group 3 demonstrated significantly worse surgical outcomes when compared to Group 1 and 2 for overall (4.0 vs. 9.1 vs. 18.9%, p < 0.001) and serious complications (1.2 vs. 4.2 vs. 8.0%, p < 0.001), length of hospital stay (2.78 vs. 3.72 vs. 5.87 days, p < 0.001), and open conversion (0.1 vs. 1.0 vs. 2.1%, p = 0.007). Incidental gallbladder cancer was also the most common in Group 3 (0.3 vs. 1.5 vs. 3.1%, p = 0.001). In the multivariate analysis, body mass index < 18.5, moderate/severe AC, and albumin < 2.5 g/dL were significant risk factors for serious complications in Group 3. CONCLUSION: Advanced age was associated with severe AC, worse surgical outcomes, and a higher rate of incidental gallbladder cancer following LC. Therefore, in patients over 80 years of age with AC, especially those with poor nutritional status and high severity grading, urgent surgery should be avoided, and surgery should be performed after sufficient supportive care to restore nutritional status before LC.

A wireless, solar-powered, optoelectronic system for spatial restriction-free long-term optogenetic neuromodulations.

Numerous wireless optogenetic systems have been reported for practical tether-free optogenetics in freely moving animals. However, most devices rely on battery-powered or coil-powered systems requiring periodic battery replacement or bulky, high-cost charging equipment with delicate antenna design. This leads to spatiotemporal constraints, such as limited experimental duration due to battery life or animals' restricted movement within specific areas to maintain wireless power transmission. In this study, we present a wireless, solar-powered, flexible optoelectronic device for neuromodulation of the complete freely behaving subject. This device provides chronic operation without battery replacement or other external settings including impedance matching technique and radio frequency generators. Our device uses high-efficiency, thin InGaP/GaAs tandem flexible photovoltaics to harvest energy from various light sources, which powers Bluetooth system to facilitate long-term, on-demand use. Observation of sustained locomotion behaviors for a month in mice via secondary motor cortex area stimulation demonstrates the notable capabilities of our device, highlighting its potential for space-free neuromodulating applications.

Association between lone work and self-rated health status: using the 5th Korean Working Conditions Survey.

Background: Lone workers are generally defined as individuals who work alone without supervision, including self-employed people. While lone workers are considered a vulnerable group in some countries, there is a lack of research on their health status in domestic studies. Globally, the number of lone workers has been increasing, and this trend has been further accelerated since the coronavirus disease 2019 (COVID-19) pandemic with the rise of remote work. Methods: The study analyzed data from 44,281 participants, excluding unpaid family workers, soldiers, and those with missing data. Lone workers were defined as individuals who reported having no colleagues with the same job at their current workplace. Self-rated health status was categorized as "good" or "poor." Results: This study found a statistically significant higher number of lone workers among women compare to men. The largest occupational category for lone workers was service and sales workers, followed by agriculture and fisheries workers. A majority of non-lone workers reported working 40 hours or less per week, while the majority of lone workers reported working 53 hours or more per week. In addition, lone workers had significantly poorer health status evaluations compared to non-lone workers (odds ratio: 1.297; 95% confidence interval: 1.165-1.444). Conclusions: Further research is needed to investigate the causal relationship between lone work and health, using data collected after the COVID-19 pandemic.